New Publication from Dr. Laurie Ailles

May 20, 2020

Isolation and transcriptional profiling of CD49e+ CAFs
MBP scientist Dr. Laurie Ailles and a team of research collaborators have published a new Journal of Experimental Medicine (JEM) article entitled 'Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21'. According to Dr. Ailles, this study "shows different subtypes of cancer-associated fibroblasts have distinct effects on aggressiveness and patient outcomes in the most common form of ovarian cancer".

Article Abstract'Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes, the roles they play in cancer progression, and molecular mediators of the CAF “state.” Here, we identify a novel cell surface pan-CAF marker, CD49e, and demonstrate that two distinct CAF states, distinguished by expression of fibroblast activation protein (FAP), coexist within the CD49e+ CAF compartment in high-grade serous ovarian cancers. We show for the first time that CAF state influences patient outcomes and that this is mediated by the ability of FAP-high, but not FAP-low, CAFs to aggressively promote proliferation, invasion and therapy resistance of cancer cells. Overexpression of the FAP-low–specific transcription factor TCF21 in FAP-high CAFs decreases their ability to promote invasion, chemoresistance, and in vivo tumor growth, indicating that it acts as a master regulator of the CAF state. Understanding CAF states in more detail could lead to better patient stratification and novel therapeutic strategies.'